The advantages of controlled release products are well known in the pharmaceutical field and include the ability to maintain a desired blood level of a medicament over a comparatively longer period of time while increasing patient compliance by reducing the number of administrations necessary to achieve the same. These advantages have been attained by a wide variety of methods. For example, different hydrogels have been described for use in controlled release medicines, some of which are synthetic, but most of which are semi-synthetic or of natural origin. A few contain both synthetic and non-synthetic material. However, some of the systems require special process and production equipment, and in addition some of these systems are susceptible to variable drug release.
Oral controlled release delivery systems should ideally be adaptable so that release rates and profiles can be matched to physiological and chronotherapeutic requirements.
Other pharmaceutical dosage forms are known in the art which provide release of a medicament at a local site for absorption into the body. For example, U.S. Pat. No. 4,829,056 (Sugden) describes a buccal tablet consisting of etorphine, at least one monosaccharide, disaccharide or a mixture thereof, and a mixture of xanthan gum and locust bean gum in a weight ratio of 3:1 to 1:1, wherein the total weight of the mono- and/or di-saccharides relative to the combined weight of the xanthan and locust bean gums is in the ratio of 20:1 to 3:1. The buccal tablet of this reference is intended to be placed between the gingival surface of the jaw and the buccal mucosa where it gels to produce a soft hydrated tablet which may be retained in position so as to provide release of etorphine for up to two hours. The buccal tablet is said to provide improved bioavailability.
U.S. Pat. No. 4,948,580 (Browning) describes a bioadhesive composition which may be employed as an oral drug delivery system and includes a freeze-dried polymer mixture formed of the copolymer poly(methyl vinyl ether/maleic anhydride) and gelatin dispersed in an ointment base. This composition is said to be useful to deliver oral mucosa active ingredients such as steroids, antifungal agents, antibacterial agents, etc.
In other instances, the active ingredient is not intended to be absorbed into the body. In such cases, local non-systemic activity is provided by the active ingredient.
For example, U.S. Pat. No. 4,597,959 (Barr) describes a cosmetic breath freshener composition in wafer form which is said to have slow release properties. The composition includes a multiplicity of microencapsulated liquid droplets of flavoring material contained in a base which has an adhesive therein.
U.S. Pat. No. 5,077,051 (Gallopo et al.) describes bioadhesive microcapsules which comprise xanthan gum, locust bean gum, a bulking agent and an active agent. These microcapsules are said to be particularly useful for delivering buffering agents to the oral cavity for anticarious purposes. The microcapsules are prepared by preparing a hot aqueous solution or suspension of the active agent; adding xanthan gum, locust bean gum and a bulking agent to form a viscous solution; and then (a) cooling and then drying the viscous solution to obtain a solid material which is then formed into microcapsules, or (b) spray-drying the viscous solution to form the microcapsules.
U.S. Pat. No. 4,915,948 (Gallopo et al.) describes a tablet which is said to have improved bio-adhesion to mucus membranes. The tablet includes a water soluble biopolymer selected from xanthan gum, a pectin and mixtures thereof, and a solid polyol having a solubility at room temperature in water greater than about 20 g/100 g solution.
U.S. Pat. Nos. 4,994,276, 5,128,143, and 5,135,757, hereby incorporated by reference, reported that a controlled release excipient which is comprised of synergistic heterodisperse polysaccharides (e.g., a heteropolysaccharide such as xanthan gum in combination with a polysaccharide gum capable of cross-linking with the heteropolysaccharide, such as locust bean gum) is capable of processing into oral solid dosage forms using either direct compression, following addition of drug and lubricant powder, conventional wet granulation, or a combination of the two. The release of the medicament from the formulations therein proceeded according to zero-order or first-order mechanisms.
The controlled release excipients disclosed in U.S. Pat. Nos. 4,994,276, 5,128,143, and 5,135,757 are commercially available under the tradename TIMERx.TM. from Edward Mendell Co., Inc., Patterson, N.Y., which is the assignee of the present invention.